多发性骨髓瘤及其前体疾病的基因组景观，这一成果由丹娜-法伯癌症研究所Irene M. Ghobrial小组经过不懈努力而取得。这一研究成果发表在2025年5月21日出版的国际学术期刊《自然—遗传学》上。

课题组研究人员收集了包括1,030名患者（218名患有前体疾病）的MM基因组数据，课题组研究人员对这些数据进行了主题化，以确定复发编码和非编码候选驱动因素以及结构变异的重要热点。研究人员对这些驱动因素进行了主题化，以定义和验证一个简单的“MM样”评分，研究人员可以通过主题化将患者的肿瘤置于向活动性疾病进展的逐渐轴上。他们的MM前体基因组图谱提供了对疾病的起始时间和细胞起源，基因组改变的获得顺序以及在转化阶段发现的突变过程的见解。综上所述，该研究组在此强调基因组测序在更好地为MM前体条件的风险评估和监测提供信息方面的潜力。

据介绍，目前仍缺乏可靠的策略来捕获从多发性骨髓瘤（MM）前驱阶段到显性疾病进展风险的患者。

附：英文原文

Title: Genomic landscape of multiple myeloma and its precursor conditions

Author: Alberge, Jean-Baptiste, Dutta, Ankit K., Poletti, Andrea, Coorens, Tim H. H., Lightbody, Elizabeth D., Toenges, Rosa, Loinaz, Xavi, Wallin, Sofia, Dunford, Andrew, Priebe, Oliver, Dagan, Johnathan, Boehner, Cody J., Horowitz, Erica, Su, Nang K., Barr, Hadley, Hevenor, Laura, Towle, Katherine, Beesam, Rashmika, Beckwith, Jenna B., Perry, Jacqueline, Cordas dos Santos, David M., Bertamini, Luca, Greipp, Patricia T., Kbler, Kirsten, Arndt, Peter F., Terragna, Carolina, Zamagni, Elena, Boyle, Eileen M., Yong, Kwee, Morgan, Gareth, Walker, Brian A., Dimopoulos, Meletios Athanasios, Kastritis, Efstathios, Hess, Julian, Sklavenitis-Pistofidis, Romanos, Stewart, Chip, Getz, Gad, Ghobrial, Irene M.

Issue&Volume: 2025-05-21

Abstract: Reliable strategies to capture patients at risk of progression from precursor stages of multiple myeloma (MM) to overt disease are still missing. We assembled a comprehensive collection of MM genomic data comprising 1,030 patients (218 with precursor conditions) that we used to identify recurrent coding and non-coding candidate drivers as well as significant hotspots of structural variation. We used those drivers to define and validate a simple ‘MM-like’ score, which we could use to place patients’ tumors on a gradual axis of progression toward active disease. Our MM precursor genomic map provides insights into the time of initiation and cell-of-origin of the disease, order of acquisition of genomic alterations and mutational processes found across the stages of transformation. Taken together, we highlight here the potential of genome sequencing to better inform risk assessment and monitoring of MM precursor conditions.

DOI: 10.1038/s41588-025-02196-0

Source: https://www.nature.com/articles/s41588-025-02196-0